Major Depressive Disorder, 1e

Cover
Major Depressive Disorder
Copyright
List of Contributors
Preface
1. A Summary of Recent Updates on the Genetic Determinants of Depression∗
	INTRODUCTION
	FINDINGS FROM GENETIC ASSOCIATION STUDIES
		Results From Genome-Wide Association Studies
		Results From Structural and Rare-Variant Association Studies
	FINDINGS FROM GENE–ENVIRONMENT INTERACTION STUDIES
	CURRENT AND FUTURE DIRECTIONS FOR RESEARCH
		Understanding the Biological Function of Loci Identified through GWAS
		Identifying Best Practices to Study Gene–Environment Interaction
		Leveraging Genetics to Strengthen Causal Inference
	CONCLUSIONS
	REFERENCES
2. Epigenetics of Major Depressive Disorder
	INTRODUCTION
	DNA METHYLATION
	TWIN STUDIES OF DEPRESSION
	THEORIES OF DEPRESSION
		Stress Model of Depression
		Neurotrophic Hypothesis of Depression
		Monoamine Hypothesis of Depression
	INFLUENCE OF OTHER EPIGENETIC MODIFICATIONS
		Histone Modifications
		Noncoding RNAs (ncRNAs)
	CONCLUSION
	REFERENCES
3. Brain Structural Abnormalities of Major Depressive Disorder
	INTRODUCTION
	REGIONAL BRAIN ABNORMALITIES
	CORTICAL REGIONS
		Frontal Lobe
		Temporal Lobe
		Parietal Lobe
	CINGULATE CORTEX
	OTHER CORTICAL REGIONS
	SUBCORTICAL REGIONS
		Hippocampus
		Amygdala
		Thalamus
		Basal Ganglia
		Cerebellum
	BRAIN STEM
	NEGATIVE FINDINGS
	WHITE MATTER
	WHITE MATTER HYPERINTENSITIES
	VOLUMETRIC STUDIES
	WM MICROSTRUCTURE
		Adults
			Areas
				Corpus callosum
		Fusiform Gyrus
		Superior Longitudinal Fasciculus
		Inferior Longitudinal Fasciculus
		Inferior Fronto-Occipital Fasciculus
		Thalamic Radiations
	GERIATRIC DEPRESSION
	CONCLUSIONS
	ABBREVIATIONS
	REFERENCES
4. Cognitive Deficits in Major Depression: From Mechanisms to Management
	INTRODUCTION
	COGNITIVE DEFICITS AND RELATED FUNCTIONAL IMPAIRMENT IN DEPRESSION
		Types of Cognitive Deficits Observed in Depression
		Measurement of Cognitive Deficits in Depression
		Effects of Cognitive Deficits on Depressed Individuals
	NEUROBIOLOGY OF COGNITIVE DEFICITS IN DEPRESSION
	PHARMACOLOGICAL TREATMENTS FOR COGNITIVE DEFICITS IN DEPRESSION
		Antidepressants
		Psychostimulants
		Other Pharmacological Agents
	NONPHARMACOLOGICAL TREATMENTS FOR COGNITIVE DEFICITS IN DEPRESSION
	DISCUSSION
	REFERENCES
5. Neuroendocrine Alterations in Major Depressive Disorder
	INTRODUCTION
	OVERVIEW OF NORMAL HPA AXIS PHYSIOLOGY
	HPA AXIS PATHOPHYSIOLOGY IN DEPRESSION
	THE CRF NEUROPEPTIDE SYSTEM
	CRF HYPOTHESIS OF DEPRESSION
	EARLY-LIFE STRESS AND DEPRESSION: HPA AXIS INVOLVEMENT
	HPA AXIS AND RESPONSE TO PSYCHOLOGICAL STRESS
	CHILDHOOD TRAUMA AND HPA AXIS CHALLENGE TESTS
	GLUCOCORTICOID INVOLVEMENT
	CSF CRF IN CHILDHOOD TRAUMA AND DEPRESSION
	THYROTROPIN-RELEASING HORMONE, THE HYPOTHALAMIC–PITUITARY–THYROID AXIS, AND DEPRESSION
	PSYCHIATRIC MANIFESTATIONS OF THYROID DYSFUNCTION
	GROWTH HORMONE, SOMATOSTATIN, AND DEPRESSION
	HYPOTHALAMIC–PROLACTIN AXIS AND DEPRESSION
	CONCLUSIONS
	FINANCIAL DISCLOSURES
	REFERENCES
6. Inflammatory Abnormalities in Major Depressive Disorder
	INTRODUCTION
	INFLAMMATION AND DEPRESSION: CAUSE AND EFFECT RELATIONSHIP, AND THE ROLE OF CYTOKINES
	MACROPHAGE THEORY OF DEPRESSION
	ROLE OF MICROGLIA IN DEPRESSION
	ROLE OF INFLAMMASOMES IN DEPRESSION
	INFLAMMATORY SYSTEMIC DISEASES AND DEPRESSION
	INFLAMMATION GENES AND DEPRESSION
	MECHANISTIC INSIGHTS INTO NEUROINFLAMMATION AND RELATED PATHWAYS DURING DEPRESSION
	ANTIINFLAMMATORY PROPERTIES OF VARIOUS INTERVENTIONS IN THE TREATMENT OF DEPRESSION
	DISCUSSION
	REFERENCES
7. Psychiatric Comorbidity in Major Depressive Disorder
	INTRODUCTION
	ANXIETY DISORDERS
	ATTENTION-DEFICIT HYPERACTIVITY DISORDER
	SUBSTANCE USE DISORDER
	PSYCHOTIC DISORDERS
	PERSONALITY DISORDERS
	CONDUCTING A GOOD PSYCHIATRIC REVIEW OF SYSTEMS
	MEASUREMENT-BASED CARE: USE IT!
	CONCLUDING REMARKS
	REFERENCES
8. Pharmacological Treatment of Major Depressive Disorder
	INTRODUCTION
	CURRENTLY APPROVED PHARMACOLOGICAL TREATMENTS OF DEPRESSION
		Monoamine Oxidase Inhibitors
		Tricyclic Antidepressants
		Selective Serotonin Reuptake Inhibitors
		Selective Serotonin and Norepinephrine Reuptake Inhibitors
		Nonserotonergic Agents—Norepinephrine and Dopamine Reuptake Inhibitors and Norepinephrine Reuptake Inhibitors
		Serotonin Antagonists/Reuptake Inhibitors
		Noradrenergic and Specific Serotonin Agents
		New and Emerging Antidepressants
		Multimodal Antidepressants—Serotonin Modulator and Stimulators
		Novel Experimental Antidepressants
	GENERAL PRINCIPLES TO THE PHARMACOLOGICAL TREATMENT OF MDD
		Comparative Efficacy and Tolerability
		Patient Factors—Clinical Features and Dimensions
	APPROACH TO TREATMENT NONRESPONSE AND TREATMENT RESISTANCE
		Adjunctive Treatments
		New and Emerging Treatment Approaches
	CONCLUSION
	REFERENCES
9. Neurocircuitry-Based Treatments for Major Depressive Disorder
	INTRODUCTION
	REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION
	CONVULSIVE THERAPIES (ELECTROCONVULSIVE THERAPY AND MAGNETIC SEIZURE THERAPY)
	SURGICAL APPROACHES TO TRD
		Deep Brain Stimulation
		Vagus Nerve Stimulation
		MRI-Guided Focused Ultrasound
	CONCLUSION
	REFERENCES
10. Pharmacological and Nonpharmacological Treatment Effects on Functional Outcomes in Major Depressive Disorder
	INTRODUCTION
	HOW IS FUNCTION IMPAIRED IN MDD?
	TREATMENT EFFECTS ON FUNCTIONAL OUTCOMES IN MDD
		Pharmacological Treatments
		Psychotherapy
		Lifestyle Interventions
		Neuromodulatory Treatments
		Trajectory of Functional Improvements during Treatment
	CURRENT LIMITATIONS IN THE FIELD AND FUTURE DIRECTIONS
	REFERENCES
11. Internet-Based/Technology-Based Interventions in Major Depressive Disorder
	INTRODUCTION
	GLOBAL IMPACT OF MOBILE TECHNOLOGY AND THE INTERNET IN HEALTHCARE
		The Role of Internet and Technology-Based Interventions in Medicine
			Patient education
			Patient monitoring
			Digital phenotyping
			Disease management
			Patient empowerment
	INTERNET AND TECHNOLOGY-BASED INTERVENTIONS IN PSYCHIATRY
		The Advantages of Digital Platforms in Psychiatry
			Remote patient monitoring in psychiatry
			Disease management and care delivery
			Digital phenotyping
	DIGITAL TECHNOLOGIES IN THE ASSESSMENT AND MANAGEMENT OF MDD
		Screening and Diagnosis of MDD
		Monitoring of MDD
			Continuous real-time data
			Objective markers of disease
		Management of MDD
			Antidepressant medication guidance
			Internet-CBT
	LIMITATIONS
	CONCLUSION
	REFERENCES
	FURTHER READING
12. Dysregulation of the Glutamatergic System in Major Depressive Disorder
	STUDIES OF CIRCULATING GLUTAMATE LEVELS
	DIRECT MEASUREMENTS OF BRAIN GLUTAMATE LEVELS
	GENETIC STUDIES
	GLUTAMATE RECEPTOR AND STRUCTURAL PROTEIN ABNORMALITIES
	IMAGING STUDIES
	REFERENCES
13. Glutamate Modulators in Major Depressive Disorder
	HOW DOES KETAMINE\'S MECHANISM OF ACTION SUPPORT THE HYPOTHESIS OF GLUTAMATE DYSREGULATION IN DEPRESSION?
	CLINICAL EFFECTS OF KETAMINE
	BEYOND KETAMINE: OTHER GLUTAMATERGIC MODULATORS AS NOVEL ANTIDEPRESSANTS
	REFERENCES
14. Depression in Children and Adolescents
	DEPRESSION IN CHILDREN AND ADOLESCENTS
		Assessment and Diagnosis
		Initial Management
			Active monitoring
			Psychoeducation
			Peer support
		Treatment
			Psychotherapy
				Interpersonal therapy for adolescents
				Cognitive behavioral therapy
			Medication
				Combination therapy
		Ongoing Management
		Summary
	REFERENCES
Index
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